Growth inhibition and chemosensitization of human carcinoma cells by human serum albumin-coated liposomal antisense oligodeoxyribonucleotide against bcl-2.

Previous study has shown human serum albumin (HSA) coated liposomes can deliver bcl-2 antisense oligodeoxyribonucleotide (ODN) into KB carcinoma cells, and decrease bcl-2 mRNA and protein expression level. In the current study, cell growth inhibition and chemosensitization of KB cells were evaluated. Liposomes composed of dimethyldioctadecyl ammonium bromide/egg phosphatidylcholine/α-tocopheryl polyethylene glycol 1000 succinate (58:40:2 molar ratio) complexed with bcl-2 antisense ODN and coated with HSA were examined for cell growth inhibition and sensitization to a commonly used chemotherapeutic drug, doxorubicin. HSA-coated liposome-ODN complexes effectively inhibited cell growth in the range of ODN concentration of 0.45-7.2 µM. Upon posttreatment with doxorubicin, the cytotoxicity was further significantly increased compared to the ODN complexes alone. The cytotoxicity was dependent on antisense ODN concentration, incubation time and doxorubicin concentration, and relatively independent on HSA concentration. This study suggests that HSA-coated liposomes are effective delivery vehicles for antisense ODN with potential therapeutic application and can be effectively combined with doxorubicin.